1. Field of the Invention
The present invention relates generally to the fields of dentistry and oral biology. More particularly, it concerns the generation of oral tissues from viable cells using ex vivo culture on a structural matrix. The regenerated oral tissues provided herein may be used in a variety of clinical applications and also in in vitro biocompatibility testing.
2. Description of Related Art
A major goal of dental research is the development of effective clinical approaches to promote the regeneration of oral tissues following various insults or diseases. While synthetic materials have been successfully utilized as restorative materials for dental tissues for a number of years (Craig, 1989), these materials do not replace the normal structure and function of the lost tissue and are incapable of remodeling/repairing in the face of ongoing insult or stimulation.
One such example is that of root canal therapy. Approximately 15 million patients in the U.S. require a root canal each year. Here, necrotic pulp tissue resulting from trauma or bacterial infection is removed and replaced with a non-viable synthetic material. The synthetic material is clearly unable to provide the biological functions of pulp tissue, and failure leads to tooth loss.
Engineering new tissues from cultured cells represents a new approach to treat patients suffering from the loss or malfunction of certain tissues (Langer and Vacanti, 1994). However, with the limited exception of oral mucosa, the techniques of cell and tissue culture have not been successfully applied in the engineering of oral tissues. Current cell culture techniques, such as those used in the regeneration of skin, and even oral mucosa, are not transferable to the regeneration of other oral tissues as the existing techniques produce epithelia which require an appropriate connective tissue bed in vivo for successful grafting. The art therefore lacks appropriate techniques for the production of tissues ex vivo that will repair and regenerate specific oral connective tissues in vivo.
Dental pulp is a loose connective tissue that provides dentinogenic, nutritive, sensory and defensive functions to the tooth (Chiego, 1994). Dentin is produced by specialized cells, odontoblasts, which reside in dental pulp. Tertiary dentinogenesis is often initiated following injury to or loss of dentin by the original odontoblasts, or if lost, by unidentified cells which differentiate into odontoblasts (Lesot et. al., 1993).
Dental pulp and other oral tissues may be capable of regenerating following injury, but the specific mechanisms underlying pulp regeneration and reparative dentinogenesis have not been identified. As there is little known about such processes, the ability to culture or regenerate dental pulp and other oral tissues has been severely hampered. The development of methodology by which to culture oral tissues would thus represent a significant breakthrough in this field.